Ianalumab Week 108 Durability Impresses but Modest Separation and Open-Label Weight Limit Verdict

Novartis' Ianalumab Shows Sustained Efficacy in Sjögren’s Disease Over Two Years

Novartis announced long-term results from the ongoing NEPTUNUS extension study of ianalumab in Sjögren’s disease, presented at the American College of Rheumatology Convergence 2026. The data demonstrated that patients continuing ianalumab 300 mg monthly experienced a sustained and deepening reduction in systemic disease activity, as measured by ESSDAI, through Week 108. Low disease activity rates increased to 65.1% in the continuous treatment group. Improvements in stimulated salivary flow and physician- and patient-reported outcomes were maintained, with no new safety findings reported through Week 204. Patients who switched from placebo to ianalumab also showed improvements across most efficacy outcomes.

• The NEPTUNUS extension study revealed that patients on continuous ianalumab 300 mg monthly achieved a mean reduction of 7.5 points in the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) from baseline by Week 108. This sustained and deepening reduction in systemic disease activity underscores ianalumab's potential for long-term disease control, addressing the chronic and systemic nature of Sjögren’s disease.
• Low disease activity (LDA) rates significantly increased from 57.1% at Week 48 to 65.1% by Week 108 in patients continuously receiving ianalumab. Additionally, improvements in stimulated salivary flow were maintained through Week 96, and physician- and patient-reported measures (ESSPRI and SSSD) showed sustained benefits, indicating comprehensive improvements in key symptoms and patient quality of life.
• The long-term data confirmed a consistent safety profile for ianalumab, with adverse event and serious adverse event rates comparable between treatment arms through Week 204 and no new safety findings. Furthermore, patients who switched from placebo to ianalumab at Week 60 demonstrated improvements across most efficacy outcomes, reinforcing the drug's therapeutic effect and tolerability over an extended period.

Addressing the Unmet Needs in Sjögren’s Disease Treatment

Current treatment for primary Sjögren syndrome remains centered on symptom relief without established disease-modifying options. Evidence from controlled trials supports topical therapies and secretagogues for sicca features, while data to guide systemic therapy remain limited and levels of evidence are mostly modest.

• No disease modification with conventional therapy: Conventionnal therapy including moisturizers, pilocarpine, cevimeline, local cyclosporine, and hydroxychloroquine remains the basis for treatment but does not modify the course of the disease, and no evidence-based therapeutic guidelines are currently available.

• Limited systemic benefit for sicca, pain and fatigue: Small trials found no significant improvement in sicca outcomes for oral prednisone or hydroxychloroquine and limited benefits for immunosuppressive agents including azathioprine and cyclosporine, with a large trial finding limited benefits for oral interferon alfa-2a. Management guidance reserves systemic treatment for systemic manifestations, with use of systemic therapies for dryness, chronic pain or fatigue not warranted.

• Lack of efficacy of anti-tumor necrosis factor agents and other biologics in randomized trials: Two placebo-controlled trials of infliximab and etanercept did not achieve the primary outcome defined as a composite visual analog scale measuring joint pain, fatigue, and dryness, and RCTs using infliximab, anakinra and baminercept found no placebo-differences for the primary outcomes.

• Inconsistent rituximab results and insensitive endpoints: The two largest RCTs randomised 255 patients to receive rituximab or placebo and reported no significant results in the primary outcome defined as VAS composite, while prospective studies suggested efficacy in systemic disease. In a randomized trial in 120 patients, rituximab did not alleviate symptoms or disease activity at week 24, although it alleviated some symptoms at earlier time points, with low disease activity at baseline and a primary outcome that may have been insensitive to detect clinically important changes cited as limitations.

• Disconnect between systemic activity and patient-reported outcomes: Double-blind prospective trials of traditional disease-modifying antirheumatic drugs and biologics have failed because they have not improved benign symptoms, the major cause of lowered quality of life. Systemic activity does not necessarily correlate with patient-reported outcomes, and both dimensions must be evaluated to capture the full spectrum of disease, with ESSDAI and ESSPRI now providing a common framework.

• Safety and tolerability constraints: Rituximab is associated with infusion-related reactions and serum sickness, including infusion reactions, serum sickness and infection, with one pilot study reporting one episode of serum sickness. Adverse events were common across pharmacological interventions, and larger controlled trials are needed to establish efficacy.

Ianalumab Shows Sustained Efficacy and Safety in Sjögren’s Disease

In real-world cohorts, rituximab demonstrated durable systemic benefit with glucocorticoid-sparing effects. In PORTRESS, ESSDAI significantly decreased from 11(6-22) to 4(0-8) at 12 months (p < .001), with a clinically meaningful response (ΔESSDAI ≥ 3) achieved in 74% of patients, while median glucocorticoid dose decreased from 5.0(0-12.5) to 0(0-5.0) mg/day (p < .001). With long-term therapy with Russian rituximab biosimilar (Acellbia), median duration of RTX therapy was 27 [19; 55] months and median total dose was 4 [3.5; 5.5] g, ESSDAI significantly decreased (from 5 [2; 8] to 1 [0; 3] points; p<0.001), minimal clinically important improvement was achieved in 66.6% of patients, and long-term therapy in most cases (60-80%) led to stabilization or improvement of SjD manifestations, including relief of recurrent parotitis in all patients and persistent enlargement of the salivary glands in 9 of 10 patients.

Irreversible damage accrual underscores the need for durable disease control. In a 5-year multicentre GIRRCS cohort of 429 patients, 48% had SSDI≥1 at baseline and 65% had cumulative damage after 5 years: ocular 34.2%, oral 21.7% and systemic 40.8%, with higher baseline ESSDAI predicting damage across all domains. In a 40-year follow-up cohort of 283 patients with mean follow-up of 12.5 ± 8.6 years, lymphoma developed in 9.9% (mostly non-Hodgkin MALT) and was associated with hypergammaglobulinemia (p = 0.03; RR = 2.56) and parotid swelling (p < 0.001; RR = 5.53), while in the French ASSESS cohort with mean follow-up of 56.4 months (±10.6), B cell biomarkers remained stable in 80.5% and patients with ≥5 abnormal B cell activity markers had increased risk of persistent or worsening disease (OR 4.6, 95% CI 1.2-17.8; p= 0.002).

For the first time 2 phase 3 studies (ianalumab and telitacicept) reported positive results, and B-cell-targeted therapies (ianalumab, telitacicept), FcRn inhibitors (nipocalimab, efgartigimod), CD40/CD40L blockade, kinase inhibitors and other immunomodulatory strategies have achieved significant improvements in ESSDAI and, in some cases EULAR Sjögren's syndrome patient reported index (ESSPRI) with an acceptable safety profile. Glandular measures also showed persistence of effect in smaller long-term studies, including significant increase in stimulated saliva flow (from 1.5 [0.5; 3] to 2.4 [1.4; 3.5] mL; p = 0.002) and stimulated Schirmer's test (from 6 [3.75; 12] to 8 [5; 15] mm; p = 0.005) during RTX biosimilar therapy, and significantly higher unstimulated whole saliva flow at 3 months, 6 months and 12 months compared to baseline after sialendoscopy (P = .002, P = .01, and P = .04 respectively).

Beyond Sjögren’s: Ianalumab's Expanding Pipeline Potential

Beyond its Sjögren’s program, ianalumab is being evaluated across additional B cell–driven autoimmune conditions, most notably systemic lupus erythematosus and immune thrombocytopenia. These trials combine BAFF receptor blockade and B cell depletion with standard background therapies to assess disease activity and durability of response.